Isolation, Structure Determination of Sesquiterpenes from Neurolaena lobata and Their Antiproliferative, Cell Cycle Arrest-Inducing and Anti-Invasive Properties against Human Cervical Tumor Cells

Andrea Vasas; Ildikó Lajter; Norbert Kúsz; Sándor Balázs Király; Tibor Kovács; Tibor Kurtán; Noémi Bózsity; Nikolett Nagy; Zsuzsanna Schelz; István Zupkó; Georg Krupitza; Richard Frisch; Attila Mándi; Judit Hohmann

doi:10.3390/pharmaceutics13122088

Isolation, Structure Determination of Sesquiterpenes from Neurolaena lobata and Their Antiproliferative, Cell Cycle Arrest-Inducing and Anti-Invasive Properties against Human Cervical Tumor Cells

Pharmaceutics. 2021 Dec 5;13(12):2088. doi: 10.3390/pharmaceutics13122088.

Authors

Affiliations

¹ Department of Pharmacognosy, Interdisciplinary Excellence Centre, University of Szeged, Eötvös u. 6., H-6720 Szeged, Hungary.
² Department of Organic Chemistry, University of Debrecen, H-4032 Debrecen, Hungary.
³ Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary.
⁴ Clinical Institute of Pathology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
⁵ Institute for Ethnobiology, Playa Diana, San José GT-170, Petén, Guatemala.
⁶ Interdisciplinary Centre of Natural Products, University of Szeged, H-6720 Szeged, Hungary.

Abstract

Seven new germacranolides (1-3, 5-8), among them a heterodimer (7), and known germacranolide (4), eudesmane (9) and isodaucane (10) sesquiterpenes were isolated from the aerial parts of Neurolaena lobata. Their structures were determined by using a combination of different spectroscopic methods, including HR-ESIMS and 1D and 2D NMR techniques supported by DFT-NMR calculations. The enantiomeric purity of the new compounds was investigated by chiral HPLC analysis, while their absolute configurations were determined by TDDFT-ECD and OR calculations. Due to the conformationally flexible macrocycles and difficulties in assigning the relative configuration, ¹³C and ¹H NMR chemical shift and ECD and OR calculations were performed on several stereoisomers of two derivatives. The isolated compounds (1-10) were shown to have noteworthy antiproliferative activities against three human cervical tumor cell line with different HPV status (HeLa, SiHa and C33A). Additionally, lobatolide C (6) exhibited substantial antiproliferative properties, antimigratory effect, and it induced cell cycle disturbance in SiHa cells.

Keywords: Asteraceae; Neurolaena lobata; SiHa cells; antimigratory effect; antiproliferative; eudesmanes; germacranolides; isodaucane; sesquiterpenes.

Abstract

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